Journal Article

Nuclear domain 10-associated proteins recognize and segregate intranuclear DNA/protein complexes to negate gene expression

Rivera-Molina, Yisel A, Rojas, Bruno R, Tang, Qiyi

2012

Overview

Background DNA viruses, such as herpes simplex virus type 1 (HSV-1), Simian virus 40 (SV40), and Cytomegaloviruses (CMV), start their replicative processes and transcription at specific nuclear domains known as ND10 (nuclear domain 10, also called PML bodies). It has been previously determined that for HSV-1 and SV40, a short DNA sequence and its binding protein are required and sufficient for cell localization of viral DNA replication and gene transcription. Results Our recent observations provide evidence that a foreign (not endogenous) DNA/protein complex in the nucleus recruits ND10 proteins. First, the complexes formed from the bacterial lac operator DNA and its binding protein (lac repressor), or from HPV11 (human papillomavirus 11) origin DNA and its binding protein (E2), co-localized with different ND10 proteins. Second, the HSV-1 amplicon without inserted lac operator DNA repeats distributed in the nucleus randomly, whereas the amplicon with lac operator DNA repeats associated with ND10, suggesting that DNA-binding proteins are required to localize at ND10. The cellular intrinsic DNA/protein complex (as detected for U2 DNA) showed no association with ND10. Furthermore, our examination of PML−/−, Daxx−/−, and Sp100-negative cells led to our discovering that DNA/protein complexes recruit ND10 protein independently. Using the GFP-LacI/Operator system, we were able to direct the transfected DNA to ND10 and found that gene expression was significantly repressed when the transfected DNA was directed to ND10. Conclusion Taken together, the results suggest that cells recognize DNA/protein complexes through a mechanism that involves interaction with the ND10-associated proteins.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Amplicon / animal viruses / Binding proteins / Biomedical and Life Sciences / Biomedicine / Cell culture / Cell Line / Cellular proteins / Cytomegalovirus / Daxx / DNA / DNA - metabolism / DNA replication / DNA sequencing / DNA viruses / DNA-binding proteins / DNA-Binding Proteins - metabolism / gene expression / Gene Expression Regulation / Genes / Genetic aspects / Genetic research / Genetic transcription / Genomes / Health sciences / Herpes simplex virus 1 / Herpesvirus 1, Human - genetics / Host-Pathogen Interactions / Human alphaherpesvirus 1 / Human papilloma virus 11 / Human papillomavirus 11 / Human papillomavirus 11 - genetics / Human papillomavirus type 6 / Humans / Hypotheses / Lac operator / Lac Operon / Lac repressor / Macaca mulatta polyomavirus 1 / Monkeys / Nuclear bodies / Nuclear domain 10 (ND10) / Nuclear Proteins - immunology / Nuclear Proteins - metabolism / nucleotide sequences / Nucleotide sequencing / Operator Regions, Genetic / Papillomavirus infections / Physiological aspects / Plasmids / PML / Protein Binding / Protein-DNA complexes / Proteins / Simian virus 40 / Simian virus 40 - genetics / Studies / Transcript location / transcription (genetics) / Virology